Ring-opened azlactone initiators for atom transfer radical polymerization

ABSTRACT

Initiators for atom transfer radical polymerizations are described. The initiators have an azlactone or ring-opened azlactone moiety to provide telechelic (co)polymers.

FIELD OF THE INVENTION

The present invention provides initiators and initiator systems for atomtransfer radical polymerization (ATRP) processes.

BACKGROUND

In conventional radical polymerization processes, the polymerizationterminates when reactive intermediates are destroyed or renderedinactive; radical generation is essentially irreversible. It isdifficult to control the molecular weight and the polydispersity(molecular weight distribution) of polymers produced by conventionalradical polymerization, and difficult to achieve a highly uniform andwell-defined product. It is also often difficult to control radicalpolymerization processes with the degree of certainty necessary inspecialized applications, such as in the preparation of end functionalpolymers, block copolymers, star (co)polymers, and other noveltopologies.

In a controlled radical polymerization process radicals are generatedreversibly, and irreversible chain transfer and chain termination areabsent. There are four major controlled radical polymerizationmethodologies: atom transfer radical polymerization (ATRP), reversibleaddition-fragmentation chain transfer (RAFT), nitroxide-mediatedpolymerization (NMP) and iniferters, each method having advantages anddisadvantages.

Atom transfer radical polymerization (ATRP) has been described as asimple, versatile and efficient controlled radical polymerizationprocess. See M. Freemantle, “In Control of a Living Process”, Chemicaland Engineering News, Sep. 9, 2002, pp. 36-40. ATRP processes typicallyemploy an alkyl halide as an initiator and a transition metal complex asa catalyst to produce a polymeric radical in the presence of a monomer.

Atom transfer radical polymerization systems based on the combination ofa transition metal halide and an alkyl halide have been described. “Atomtransfer” refers to the transfer of the halogen atom between thetransition metal and the polymer chain. For example, K. Matyjaszewski,(Macromolecules, vol. 28, 1995, pp. 7901-7910 and WO 96/30421) describesthe use of CuX (where X=Cl, Br) in conjunction with bipyridine and analkyl halide to give polymers of narrow molecular weight distributionand controlled molecular weight. A comprehensive review of ATRP isprovided by Matyjaszewski and Xia, Chem. Rev., vol. 101, pp. 2921-2990,2001.

Thus, there is a need for a radical polymerization process whichprovides (co)polymers having a predictable molecular weight and a narrowmolecular weight distribution (low “polydispersity”). A further need isstrongly felt for a radical polymerization process which is sufficientlyflexible to provide a wide variety of products, but which can becontrolled to the degree necessary to provide highly uniform productswith a controlled structure (i.e., controllable topology, composition,stereoregularity, etc.). There is further need for a controlled radicalpolymerization process which provides telechelic (co)polymers capable ofentering into further polymerization or functionalization throughreactive end-groups, particularly electrophilic end groups.

SUMMARY OF THE INVENTION

The present invention provides initiators for atom transfer radicalpolymerization processes that comprise compounds of the formula:

wherein X is Cl, Br, or a pseudohalogen group;

-   R¹ and R² are each independently selected from X, H, an alkyl group,    a cycloalkyl group, a heterocyclic group, an arenyl group and an    aryl group, or R¹ and R² taken together with the carbon to which    they are attached form a carbocyclic ring;-   R³ and R⁴ are each independently selected from an alkyl group, a    cycloalkyl group, an aryl group, an arenyl group, or R³ and R⁴ taken    together with the carbon to which they are attached form a    carbocyclic ring;-   Q is a linking group selected from a covalent bond, (—CH₂—)_(o),    —CO—O—(CH₂)_(o)—, —CO—O—(CH₂CH₂O)_(o)—, —CO—NR⁶—(CH₂)_(o)—,    —CO—S—(CH₂)_(o)—, where o is 1 to 12, and R⁶ is H, an alkyl group, a    cycloalkyl group or an aryl group; and-   n is 0 or 1.

The present invention also provides initiators that comprise thering-opened reaction product of the initiators of Formula I and areactive compound, such as an aliphatic compound, having one or morenucleophilic groups. Such initiators have the general formula:

wherein

-   -   X is Cl, Br, or a pseudohalogen group;    -   R¹ and R² are each independently selected from X, H, an alkyl        group, a cycloalkyl group, an arenyl group, a heterocyclic group        and an aryl group or R¹ and R² taken together with the carbon to        which they are attached form a carbocyclic ring;    -   R³ and R⁴ are each independently selected from an alkyl group, a        cycloalkyl group, an aryl, an arenyl group, or R³ and R⁴ taken        together with the carbon to which they are attached form a        carbocyclic ring;    -   n is 0 or 1;    -   Z is O, S or NR⁶, wherein R⁶ is H, an alkyl group, a cycloalkyl        group, an arenyl group, a heterocyclic group or an aryl group;    -   R⁵ is an organic or inorganic moiety and has a valency of m, R⁵        is the residue of a mono- or polyfunctional compound of the        formula R⁵(ZH)_(m);    -   Q is a linking group selected from a covalent bond, (—CH₂—)_(o),        —CO—O—(CH₂)_(o)—, —CO—O—(CH₂CH₂O)_(o)—, —CO—NR⁶—(CH₂)_(o)—,        —CO—S—(CH₂)_(o)—, where o is 1 to 12, and R⁶ is H, an alkyl        group, a cycloalkyl group, an arenyl group, a heterocyclic group        or an aryl group;    -   m is an integer of at least 1, preferably at least 2.

In another aspect, the present invention provides an initiator systemfor controlled radical polymerization comprising the above-describedinitiators and a transition metal compound that participates in areversible redox cycle.

The initiators, and initiator systems of the present invention provide(co)polymers having a predictable molecular weight and a narrowmolecular weight distribution. Advantageously, the initiators providenovel multireactive addition polymers having first and second terminalreactive groups that may be used for further functionalization. Thepresent invention further provides a controlled radical polymerizationprocess useful in the preparation of terminal-functionalized(telechelic) (co)polymers, block copolymers, star (co)polymers, graftcopolymers, and comb copolymers. The process provides these (co)polymerswith controlled topologies and compositions.

The control over molecular weight and functionality obtained in thisinvention allows one to synthesize numerous materials with many noveltopologies for applications in coatings, surface modifications,elastomers, sealants, lubricants, pigments, personal care compositions,composites, inks, adhesives, water treatment materials, hydrogels,imaging materials, telechelic materials and the like.

In another aspect, the invention provides a method for polymerization ofone or more olefinically unsaturated monomers comprising additionpolymerizing one or more olefinically unsaturated monomers using theinitiator system comprising the azlactone initiators, or the ring-openedazlactone initiator and a transition metal compound that participates ina reversible redox cycle.

It is to be understood that the recitation of numerical ranges byendpoints includes all numbers and fractions subsumed within that range(e.g. 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5).

It is to be understood that all numbers and fractions thereof arepresumed to be modified by the term “about.”

It is to be understood that “a” as used herein includes both thesingular and plural.

The general definitions used herein have the following meanings withinthe scope of the present invention.

The term “alkyl” refers to straight or branched, cyclic or acyclichydrocarbon radicals, such as methyl, ethyl, propyl, butyl, octyl,isopropyl, tert-butyl, sec-pentyl, cyclohexyl, and the like. Alkylgroups include, for example, 1 to 18 carbon atoms, preferably 1 to 12carbon atoms, or most preferably 1 to 6 carbon atoms.

The term “aryl” means the monovalent residue remaining after removal ofone hydrogen atom from an aromatic compound which can consist of onering or two fused or catenated rings having 6 to 12 carbon atoms.

The term “arenyl” means the monovalent residue remaining after removalof a hydrogen atom from the alkyl portion of a hydrocarbon containingboth alkyl and aryl groups having 6 to 26 atoms.

The term “azlactone” means 2-oxazolin-5-one groups and 2-oxazolin-6-onegroups of Formula I, where n is 0 and 1, respectively.

The term “heterocyclic group” or “heterocycle” means the monovalentresidue remaining after removal of one hydrogen atom from ancycloaliphatic or aromatic compound having one ring or two fused ringshaving 5 to 12 ring atoms and 1 to 3 heteroatoms selected from S, N, andnonperoxidic O. Useful heterocycles include azlactone, pyrrole, furan,thiophene, imidazole, pyrazole, thiazole, oxazole, pyridine, piperazine,piperidine, hydrogenated and partially hydrogenated derivatives thereof.

The term “multifunctional” means the presence of more than one of thesame functional reactive group;

The term “multireactive” means the presence of two or more of twodifferent functional reactive groups;

The term “polyfunctional” is inclusive of multireactive andmultifunctional.

The term “acid catalyst” or “acid catalyzed” means catalysis by aBrønsted- or Lewis-acid species;

The term “molecular weight” means number average molecular weight(M_(n)), unless otherwise specified.

The term “pseudohalogen” refers to polyatomic anions that resemblehalide ions in both their acid-base and redox chemistry and haverelatively low basicity generally, and form a free radical under ATRPconditions. Useful psuedohalogens include, for example, cyanide,cyanate, thiocyanate, thiosulfate, sulfonyl halides and azide ions.

The term (co)polymer refers to homo- and copolymers.

The term (meth)acrylate refers to both methacrylate and acrylate.

DETAILED DESCRIPTION

The present invention provides novel initiators of Formula I and thecorresponding ring-opened initiators of Formula II for controlledradical polymerization processes.

wherein

-   X is Cl, Br, or a pseudohalogen group,-   R¹ and R² are each independently selected from X, H, an alkyl group    of 1 to 18 carbon atoms, a cycloalkyl group having 3 to 14 carbon    atoms, an aryl group having 6 to 12 ring atoms, an arenyl group    having 6 to 26 carbon atoms, a heterocyclic group having one ring or    two fused rings having 5 to 12 ring atoms and 1 to 3 heteroatoms    selected from S, N, and nonperoxidic O; or R¹ and R² taken together    with the carbon to which they are attached form a carbocyclic ring    containing 4 to 12 ring atoms.-   R³ and R⁴ are each independently selected from an alkyl group having    1 to 18 carbon atoms, a cycloalkyl group having 3 to 14 carbon    atoms, an aryl group having 5 to 12 ring atoms, an arenyl group    having 6 to 26 carbon atoms and 0 to 3 S, N, and nonperoxidic O    heteroatoms, or R³ and R⁴ taken together with the carbon to which    they are attached form a carbocyclic ring containing 4 to 12 ring    atoms;-   Z is O, NH, S or NR⁶, wherein R⁶ is a H, an alkyl group, an aryl    group and arenyl group or a heterocyclic group;-   R⁵ is an organic or inorganic moiety and has a valency of m;-   m is an integer of at least 1, preferably 1 to 8, most preferably at    least 2;-   Q is a linking group selected from a covalent bond, (—CH₂—)_(o),    —CO—O—(CH₂)_(o)—, —CO—O—(CH₂CH₂O)_(o)—, —CO—NR⁶—(CH₂)_(o)—,    —CO—S—(CH₂)_(o)—, where o is 1 to 12, and R⁶ is is H, an alkyl    group, a cycloalkyl group or an aryl group;-   and n is 0 or 1.

The present invention also provides initiator systems for controlledradical polymerization comprising the initiators of Formulas I and/or IIand a transition metal compound that participates in a reversible redoxcycle, e.g. Cu^(I)

Cu^(II). Useful transition metal compounds have the general formula

[ML_(p)]^(n+)A⁻, wherein M is a transition metal, generally in a lowvalency state,

L is a ligand, A− is an anion, n is the formal charge on the transitionmetal having a whole number value of 1 to 7, preferably 1 to 3, and p isthe number of ligands on the transition metal having an number value of1 to 9, preferably 1 to 2.

Useful transition metals, M^(n+), include the low valent states of Cu,Fe, Ru, Cr, Mo, Pd, Ni, Pt, Mn, Rh, Re, Co, V, Zn, Au, Nb and Ag.Preferred low valent metals include Cu(I), Fe(II), Co(II), Ru(II) andNi(II). Other valent states of these same metals may be used, and theactive low valent state generated in situ.

Useful anions, A⁻, include halogen, C₁-C₆-alkoxy, NO₃ ²⁻, SO₄ ²⁻, PO₄³⁻, IIPO₄ ²⁻, PF₆ ⁻, triflate, hexafluorophosphate, methanesulfonate,arylsulfonate, CN⁻ and alkyl carboxylates and aryl carboxylates.

The ligand, L, is used to solubilize the transition metal salts in asuitable solvent and adjust the redox potential of the transition metalfor appropriate reactivity and selectivity. The ligands can direct themetal complex to undergo the desired one-electron atom transfer process,rather than a two-electron process such as oxidative addition/reductiveelimination. The ligands may further enhance the stability of thecomplexes in the presence of different monomers, solvents or atdifferent temperatures. Acidic monomers and monomers that stronglycomplex transition metals may still be efficiently polymerized byappropriate selection of ligands.

Useful ligands include those having one or more nitrogen, oxygen,phosphorus and/or sulfur atoms which can coordinate to the transitionmetal through a σ-bond, ligands containing two or more carbon atomswhich can coordinate to the transition metal through a π-bond, andligands which can coordinate to the transition metal through a μ-bond oran η-bond.

Useful ligands include those having one or more nitrogen, oxygen,phosphorus and/or sulfur atoms which can coordinate to the transitionmetal through a σ-bond are provided by monodentate and polydentatecompounds preferably containing up to about 30 carbon atoms and up to 10hetero atoms selected from aluminum, boron, nitrogen, sulfur,non-peroxidic oxygen, phosphorus, arsenic, selenium, antimony, andtellurium, where upon addition to the metal atom, following loss ofzero, one, or two hydrogens, the polydentate compounds preferablyforming with the metal, M^(n+), a 4-, 5-, or 6-membered saturated orunsaturated ring. Examples of suitable monodentate compounds or groupsare carbon monoxide, alcohols such as ethanol, butanol, and phenol;pyridine, nitrosonium (i.e., NO⁺); compounds of Group Vb elements suchas ammonia, phosphine, trimethylamine, trimethylphosphine,tributylphosphine, triphenylamine, triphenylphosphine, triphenylarsine,tributylphosphite; nitriles such as acetonitrile, benzonitrile;isonitriles such as phenylisonitrile, butylisonitrile; carbene groupssuch as ethoxymethylcarbene, dithiomethoxycarbene; alkylidenes such asmethylidene and ethylidene.

Suitable polydentate compounds or groups include dipyridyl,1,2-bis(diphenylphosphino)ethane, 1,2-bis(diphenylarsino)ethane,bis(diphenylphosphino)methane, polyamines such as ethylenediamine,propylenediamine, tetramethyl ethylene diamine, hexamethyltris-aminoethylamine, diethylenetriamine, 1,3-diisocyanopropane, andhydridotripyrazolylborate; the hydroxycarboxylic acids such as glycolicacid, lactic acid, salicylic acid; polyhydric phenols such as catecholand 2,2′-dihydroxybiphenyl; hydroxyamines such as ethanolamine,propanolamine, and 2-aminophenol; dithiocarbamates such asdiethyldithiocarbamate, dibenzyldithiocarbamate; xanthates such as ethylxanthate, phenyl xanthate; the dithiolenes such asbis(perfluoromethyl)-1,2-dithiolene; aminocarboxylic acids such asalanine, glycine and o-aminobenzoic acid; dicarboxylic diamines asoxalamide, biuret; diketones such as 2,4-pentanedione; hydroxyketonessuch as 2-hydroxyacetophenone; alpha-hydroxyoximes such assalicylaldoxime; ketoximes such as benzil oxime; 1,10-phenanthroline,porphyrin, cryptands and crown ethers, such as 18-crown-6 and glyoximessuch as dimethylglyoxime.

Other suitable ligands that can coordinate to the transition metalthrough a σ-bond are the inorganic groups such as, for example, F⁻, OH⁻,Cl⁻, Br⁻, I⁻, and H⁻ and the organic groups such as, for example, CN⁻,SCN⁻, acetoxy, formyloxy, benzoyloxy, and the like. The ligand can alsobe a unit of a polymer; for example the amino group inpoly(ethyleneamine); the phosphino group inpoly(4-vinylphenyldiphenylphosphine); the carboxylic acid group inpoly(acrylic acid); and the isonitrile group inpoly(4-vinylphenylisonitrile).

Useful ligands containing two or more carbon atoms which can coordinateto the transition metal through a π-bond are provided by any monomericor polymeric compound having an accessible unsaturated group, i.e., anethylenic, —C═C— group; acetylenic, —C≡C— group; or aromatic group whichhas accessible π-electrons regardless of the total molecular weight ofthe compound.

Illustrative of π-bond ligands are the linear and cyclic ethylenic andacetylenic compounds having less than 100 carbon atoms (when monomeric),preferably having less than 60 carbon atoms, and from zero to 10 heteroatoms selected from nitrogen, sulfur, non-peroxidic oxygen, phosphorous,arsenic, selenium, boron, aluminum, antimony, tellurium, silicon,germanium, and tin, the ligands being those such as ethylene, acetylene,propylene, methylacetylene, α-butene, 2-butene, diacetylene, butadiene,1,2-dimethylacetylene, cyclobutene, pentene, cyclopentene, hexene,cyclohexene, 1,3-cyclohexadiene, cyclopentadiene, 1,4-cyclohexadiene,cycloheptene, 1-octene, 4-octene, 3,4-dimethyl-3-hexene, and 1-decene;η³-allyl, η³-pentenyl, norbornadiene, η⁵-cyclohexadienyl,cycloheptatriene, cyclooctatetraene, and substituted and unsubstitutedcarbocyclic and heterocyclic aromatic ligands having up to 25 rings andup to 100 carbon atoms and up to 10 hetero atoms selected from nitrogen,sulfur, non-peroxidic oxygen, phosphorus, arsenic, selenium, boron,aluminum, antimony, tellurium, silicon, germanium, and tin, such as, forexample, η⁵-cyclopentadienyl, benzene, mesitylene, toluene, xylene,tetramethylbenzene, hexamethylbenzene, fluorene, naphthalene,anthracene, chrysene, pyrene, η⁷-cycloheptatrienyl, triphenylmethane,paracyclophane, 1,4-diphenylbutane, η⁵-pyrrole, η⁵-thiophene, η⁵-furan,pyridine, gamma-picoline, quinaldine, benzopyrane, thiocihrome,benzoxazine, indole, acridine, carbazole, triphenylene, silabenzene,arsabenzene, stibabenzene, 2,4,6-triphenylphosphabenzene,η⁵-selenophene, dibenzostannepine, η⁵-tellurophene, phenothiazine,selenanthrene, phenoxaphosphine, phenarsazine, phenatellurazine,η⁵-methylcyclopentadienyl, η⁵-pentamethylcyclopentadienyl, and1-phenylborabenzene. Other suitable aromatic compounds can be found byconsulting any of many chemical handbooks.

Preferred ligands include unsubstituted and substituted pyridines andbipyridines, tertiary amines, including polydentate amines such astetramethyl ethylenediamine and hexamethyl tris-aminoethylamine,acetonitrile, phosphites such as (CH₃O)₃P, 1,10-phenanthroline,porphyrin, cryptands and crown ethers, such as 18-crown-6. The mostpreferred ligands are polydentate amines, bipyridine and phosphites.Useful ligands and ligand-metal complexes useful in the initiatorsystems of the present invention are described in Matyjaszewski and Xia,Chem. Rev., vol. 101, pp. 2921-2990, 2001.

Examples of olefinically unsaturated monomers that may be polymerizedinclude (meth)acrylates such as ethyl (meth)acrylate, propyl(meth)acrylate, butyl (meth)acrylate, isooctyl (meth)acrylate and otheralkyl (meth)acrylates; also functionalized (meth)acrylates includingglycidyl (meth)acrylate, trimethoxysilyl propyl (meth)acrylate, allyl(meth)acrylate, hydroxyethyl (meth)acrylate, hydroxypropyl(meth)acrylate, dialkylaminoalkyl (meth)acrylates; fluoroalkyl(meth)acrylates; (meth)acrylic acid, fumaric acid (and esters), itaconicacid (and esters), maleic anhydride; styrene, α-methyl styrene; vinylhalides such as vinyl chloride and vinyl fluoride; acrylonitrile,methacrylonitrile; vinylidene halides; butadienes; unsaturatedalkylsulphonic acids or derivatives thereof;2-vinyl-4,4-dimethylazlactone, and (meth)acrylamide or derivativesthereof. Mixtures of such monomers may be used.

Initiators of Formula I may be prepared using the generalized sequenceas shown:

In the above scheme, an amino acid is first acylated, generally bydissolving the amino acid in aqueous base, followed by treatment withthe acyl halide compound under interfacial reaction conditions.Cyclization may be effected by treatment with acetic anhydride andpyridine, by treatment with carbodiimides, or preferably by treatmentwith ethyl chloroformate and a trialkylamine, which proceeds through amixed carboxylic-carbonic anhydride. Further details regarding thepreparation of azlactones may be found in “Polyazlactones”, Encyclopediaof Polymer Science and Engineering, vol. 11, 2^(nd) Ed., John Wiley andSons, pp. 558-571 (1988). With respect to the above reaction scheme, itwill be apparent that diacyl halide starting materials may be used toproduce dimeric or bis-azlactone initiators, some examples of which areshown below. These bis-azlactone initiators have the general structure:

wherein

-   X is Cl, Br, or a pseudohalogen group,-   R¹ is selected from X, H, an alkyl group of 1 to 18 carbon atoms, a    cycloalkyl group having 3 to 14 carbon atoms, an aryl group having 6    to 12 ring atoms, an arenyl group having 6 to 26 carbon atoms, a    heterocyclic group having one ring or two fused rings having 5 to 12    ring atoms and 1 to 3 heteroatoms selected from S, N, and    nonperoxidic O;-   R³ and R⁴ are each independently selected from an alkyl group having    1 to 18 carbon atoms, a cycloalkyl group having 3 to 14 carbon    atoms, an aryl group having 5 to 12 ring atoms, an arenyl group    having 6 to 26 carbon atoms and 0 to 3 S, N, and nonperoxidic O    heteroatoms, or R³ and R⁴ taken together with the carbon to which    they are attached form a carbocyclic ring containing 4 to 12 ring    atoms;-   R⁷ is a divalent alkylene group of 1 to 18 carbon atoms, a    cycloalkylene group having 3 to 14 carbon atoms, an aryl group    having 6 to 12 ring atoms, or an arenyl group having 6 to 26 carbon    atoms,-   Q is a linking group selected from a covalent bond, (—CH₂—)_(o),    —CO—O—(CH₂)_(o)—, —CO—O—(CH₂CH₂O)_(o)—, —CO—NR⁶—(CH₂)_(o)—,    —CO—S—(CH₂)_(o)—, where o is 1 to 12, and R⁶ is is H, an alkyl    group, a cycloalkyl group, an arenyl group, a heterocyclic group or    an aryl group;-   and n is 0 or 1.

Useful azlactone initiators include the following compounds:

It will be understood that the above-depicted compounds may be modifiedas described in Formula I. For example, the bromine atom may besubstituted for a chlorine, fluorine or pseudohalogen group.

Ring-opened azlactone compounds of Formula II may be made bynucleophilic addition of a compound of the formula R⁵(ZH)_(m) to theazlactone carbonyl of Formula I as shown below. In the Scheme below, R⁵is an inorganic or organic group having one or a plurality ofnucleophilic -ZH groups, which are capable of reacting with theazlactone moiety of Formula I. R⁵(ZH)_(m) may be water.

If organic, R⁵ may be a polymeric or non-polymeric organic group thathas a valence of m and is the residue of a nucleophilicgroup-substituted compound, R⁵(ZH)_(m), in which Z is —O—, —S—, or —NR⁶wherein R⁶ can be a H, an alkyl, a cycloalkyl or aryl, a heterocyclicgroup, an arenyl and m is at least one, preferably at least 2. Theorganic moiety R⁵ has a molecular weight up to 20,000, preferablyselected from mono- and polyvalent hydrocarbyl (i.e., aliphatic and arylcompounds having 1 to 30 carbon atoms and optionally zero to fourcatenary heteroatoms of oxygen, nitrogen or sulfur), polyolefin,polyoxyalkylene, polyester, polyolefin, polyacrylate, or polysiloxanebackbones. If inorganic, R⁵ may comprise silica, alumina or glass havingone or a plurality of -ZH groups on the surface.

In one embodiment, R⁵ comprises a non-polymeric aliphatic,cycloaliphatic, aromatic or alkyl-substituted aromatic moiety havingfrom 1 to 30 carbon atoms. In another embodiment, R⁵ comprises apolyoxyalkylene, polyester, polyolefin, polyacrylate, or polysiloxanepolymer having pendent or terminal reactive -ZH groups. Useful polymersinclude, for example, hydroxyl, thiol or amino terminated polyethylenesor polypropylenes, hydroxyl, thiol or amino terminated poly(alkyleneoxides) and polyacylates having pendant reactive functional groups, suchas hydroxyethyl acrylate polymers and copolymers.

Depending on the nature of the functional group(s) of R⁵(ZH)_(m), acatalyst may be added to effect the condensation reaction. Normally,primary amine groups do not require catalysts to achieve an effectiverate. Acid catalysts such as trifluoroacetic, ethanesulfonic, andtoluenesulfonic acids are effective with hydroxyl groups and secondaryamines.

With respect to the compound R⁵(ZH)_(m), m is at least one, butpreferably m is at least two. The multiple -ZH groups of thepolyfunctional compound may be the same or different. Multifunctionalcompounds may be reacted with the azlactone compound of Formula I toproduce polyfunctional initiators of Formula II, where m is at leasttwo. Such polyfunctional initiators allow the preparation of graft, andstar (co)polymers and other useful topologies.

Useful alcohols of the formula R⁵(ZH)_(m) include aliphatic and aromaticmonoalcohols and polyols. Useful monoalcohols include methanol, ethanol,octanol, decanol, and phenol. The polyols useful in the presentinvention include aliphatic or aromatic polyols having 1 to 30 carbonatoms, at least two hydroxyl groups. Example of useful polyols includeethylene glycol, propylene glycol, butanediol, 1,3-pentane diol,2,2-oxydiethanol hexanediol poly(pentyleneadipate glycol),poly(tetramethylene ether glycol), poly(ethylene glycol),poly(caprolactone diol), poly(1,2-butylene oxide glycol), trimethylyolethane, trimethylol propane, trimethyol aminomethane, ethylene glycol,2-butene-1,4-diol, pentaerythritol, dipentaerythritol, andtripentaerythritol. The term “polyol” also includes derivatives of theabove-described polyols such as the reaction product of the polyol withdi- or poly-isocyanate, or di- or poly-carboxylic acid, the molar ratioof polyol to —NCO, or —COOH being 1 to 1.

Useful amines of the formula R⁵(ZH)_(m) include aliphatic and aromaticmonoamines and polyamines. Any primary or secondary amine may beemployed, although primary amines are preferred to secondary amines.Useful monoamines include, for example, methyl-ethyl-, propyl-, hexyl-,octyl, dodecyl-, dimethyl-, methyl ethyl-, and aniline. The term “di-,or polyamine,” refers to organic compounds containing at least twonon-tertiary amine groups. Aliphatic, aromatic, cycloaliphatic, andoligomeric di- and polyamines all are considered useful in the practiceof the invention. Representative of the classes of useful di- orpolyamines are 4,4′-methylene dianiline,3,9-bis(3-aminopropyl)-2,4,8,10-tetraoxaspiro[5,5]undecane, andpolyoxyethylenediamine. Many di- and polyamines, such as those justnamed, are available commercially, for example, those available fromHuntsman Chemical, Houston, Tex. The most preferred di- or polyaminesinclude aliphatic diamines or aliphatic di- or polyamines and morespecifically compounds with two primary amino groups, such as ethylenediamine, hexamethylene diamine, dodecanediamine, and the like.

Useful thiols of the formula R⁵(ZH)_(m) include aliphatic and aromaticmonothiols and polythiols Useful alkyl thiols include methyl, ethyl andbutyl thiol, as well as 2-mercaptoethanol, 3-mercapto-1,2-propanediol,4-mercaptobutanol, mercaptoundecanol, 2-mercaptoethylamine,2,3-dimercaptopropanol, 3-mercaptopropyltrimethoxysilane,2-chloroethanethiol, 2-amino-3-mercaptopropionic acid, dodecylmercaptan, thiophenol, 2-mercaptoethyl ether, and pentaerythritoltetrathioglycolate. Useful soluble, high molecular weight thiols includepolyethylene glycol di(2-mercaptoacetate), LP-3™ resins supplied byMorton Thiokol Inc. (Trenton, N.J.), and Permapol P3™ resins supplied byProducts Research & Chemical Corp. (Glendale, Calif.) and compounds suchas the adduct of 2-mercaptoethylamine and caprolactam.

The invention provides multifunctional initiators of Formula II, wherebyan azlactone initiator of Formula I is ring-opened by a multireactive ormultifunctional compound of the formula R⁵(ZH)_(m), where m is at least2. Such multifunctional initiators may be used to produce branched, starand graft (co)polymers and other topologies. It will also be apparentthat such (co)polymers may also be prepared by first polymerizing amonomer using the initiator of Formula I, to produce polymers having anazlactone group at one terminal end, and then subsequently reacting thepolymers with a polyfunctional compound of the formula R⁵(ZH)_(m), wherem is at least 2.

In another embodiment, the multifunctional initiators may comprise asolid support having a plurality of initiator moieties on the surfacethereof. Such initiator-functionalized supports have the generalstructure (corresponding to Formula II):

Wherein X, R¹, R², R³, R⁴, Z, n and m are as previously described forFormula II and SS is a solid support corresponding to R⁵. The solidsupport material includes functional groups to which initiator moleculesof Formula I can be covalently attached for building large or smallorganic compounds. Useful functional groups include hydroxyl, amino andthiol functional groups corresponding to -ZH.

The support material can be organic or inorganic. It can be in the formof solids, gels, glasses, etc. It can be in the form of a plurality ofparticles (e.g., beads, pellets, or microspheres), fibers, a membrane(e.g., sheet or film), a disc, a ring, a tube, or a rod, for example.Preferably, it is in the form of a plurality of particles or a membrane.It can be swellable or non-swellable and porous or nonporous.

The support material can be a polymeric material that can be used inconventional solid phase synthesis. It is chosen such that it isgenerally insoluble in the solvents or other components used insynthetic reactions that occur during the course of solid phasesynthesis.

Examples of useable pre-existing support materials are described in G.B. Fields et al., Int. J. Peptide Protein Res., 35, 161 (1990) and G. B.Fields et al., in Synthetic Peptides: A User's Guide, G. A. Grant, Ed.,pages 77-183, W.H. Freeman and Co., New York, N.Y. (1992). The supportmaterial is in the form of an organic polymeric material, such aspolystyrenes, polyalkylenes, nylons, polysulfones, polyacrylates,polycarbonates, polyesters, polyimides, polyurethanes, etc. and havinghydroxyl, amino or thiol substituents on the surface. For pre-existingsupport materials, a preferred support material is polystyrene.

In the present polymerization, the amounts and relative proportions ofinitiator, transition metal compound and ligand are those effective toconduct atom transfer radical polymerization (ATRP). Initiatorefficiencies with the present initiator system (initiator/transitionmetal compound/ligand system) are generally very good (at least 50%,preferably greater than 80%, more preferably greater than 90%).Accordingly, the amount of initiator can be selected such that theinitiator concentration is from 10⁻⁴ M to 1M, preferably 10⁻³ to 10⁻¹ M.Alternatively, the initiator can be present in a molar ratio of from10⁻⁴:1 to 10⁻¹:1, preferably from 10⁻³:1 to 5×10⁻²:1, relative tomonomer. The initiator system will generate, during polymerization, theredox conjugate of the transition metal compound in an amount sufficientto reversibly deactivate some portion of radicals formed in a reactionbetween said initiator, said transition metal compound and a radicallypolymerizable monomer.

The molar proportion of transition metal compound relative to initiatoris generally that which is effective to polymerize the selectedmonomer(s), but may be from 0.001:1 to 10:1, preferably from 0.1:1 to5:1, more preferably from 0.3:1 to 2:1, and most preferably from 0.9:1to 1.1:1. Conducting the polymerization in a homogeneous system maypermit reducing the concentration of transition metal and ligand suchthat the molar proportion of transition metal compound to initiator isas low as 0.0001:1.

Similarly, the molar proportion of ligand relative to transition metalcompound is generally that which is effective to polymerize the selectedmonomer(s), but can depend upon the number of coordination sites on thetransition metal compound that the selected ligand will occupy. Theamount of ligand may be selected such that the ratio of coordinationsites on the transition metal compound to coordination sites which theligand will occupy is from 0.1:1 to 100:1, preferably from 0.2:1 to10:1, more preferably from 0.5:1 to 3:1, and most preferably from 0.5:1to 2:1. It is possible for a solvent or for a monomer to act as aligand.

The present polymerization may be conducted in bulk, or in a solvent.Solvents, preferably organic, can be used to assist in the dissolutionof the initiator and initiator system in the polymerizable monomers, andas a processing aid. Preferably, such solvents are not reactive with theazlactone group. It may be advantageous to prepare a concentratedsolution of the transition metal complex in a small amount of solvent tosimplify the preparation of the polymerizable composition. Suitablesolvents include ethers such as diethyl ether, ethyl propyl ether,dipropyl ether, methyl t-butyl ether, di-t-butyl ether, glyme(dimethoxyethane), diglyme, diethylene glycol dimethyl ether; cyclicethers such as tetrahydrofuran and dioxane; alkanes; cycloalkanes;aromatic hydrocarbon solvents such as benzene, toluene, o-xylene,m-xylene, p-xylene; halogenated hydrocarbon solvents; acetonitrile;lactones such as butyrolactone, and valerolactones; ketones such asacetone, methyl ethyl ketone, methyl isobutyl ketone, cyclopentanone,and cyclohexanone; sulfones such as tetramethylene sulfone,3-methylsulfolane, 2,4-dimethylsulfolane, butadiene sulfone, methylsulfone, ethyl sulfone, propyl sulfone, butyl sulfone, methyl vinylsulfone, 2-(methylsulfonyl) ethanol, and 2,2′-sulfonyldiethanol;sulfoxides such as dimethyl sulfoxide; cyclic carbonates such aspropylene carbonate, ethylene carbonate and vinylene carbonate;carboxylic acid esters such as ethyl acetate, Methyl Cellosolve™ andmethyl formate; and other solvents such as methylene chloride,nitromethane, acetonitrile, glycol sulfite and 1,2-dimethoxyethane(glyme), mixtures of such solvents, and supercritical solvents (such asCO₂). The present polymerization may also be conducted in accordancewith known suspension, emulsion and precipitation polymerizationprocesses.

The polymerization reaction may be controlled by matching the reactivityof the groups in the initiator with the monomer, and by matching theenergetics of bond breaking and bond forming in dormant species, e.g.,dormant polymer chains and transition metal species. Matching thereactivities of the initiator with the monomer depends to some degree onthe radical stabilizing effects of the substituents. Thus, where themonomer is a halogenated alkene, one may select an initiator where of R¹and/or R² are lower alkyl groups. On the other hand, if one wishes topolymerize an arene- or ester-stabilized monomer (e.g., a(meth)acrylate, acrylonitrile or styrene), one may select an initiatorwhich is stabilized by a similar group, wherein one of R¹ and/or R² isaryl, or arenyl. Such matching of substituents on the initiator andmonomer provides a beneficial balance of the relative reactivities ofthe initiator and monomer.

Preferably, the monomer, initiator, transition metal compound and ligandare selected such that the rate of initiation is not less than 1,000times (preferably not less than 100 times) slower than the rate ofpropagation and/or transfer of the X group to the polymer radical. Inthe present application, “propagation” refers to the reaction of apolymer radical with a monomer to form a polymer-monomer adductradicals.

Polymerizing may be conducted at a temperature of from −78 to 200° C.,preferably from 0 to 160° C. and most preferably from 20 to 140° C. Thereaction should be conducted for a length of time sufficient to convertat least 10% (preferably at least 50%, more preferably at least 75% andmost preferably at least 90%) of the monomer to polymer. Typically, thereaction time will be from several minutes to 5 days, preferably from 30minutes to 3 days, and most preferably from 1 to 24 hours.

Polymerizing may be conducted at a pressure of from 0.1 to 100atmospheres, preferably from 1 to 50 atmospheres and most preferably atambient pressure (although the pressure may not be measurable directlyif conducted in a sealed vessel). An inert gas such as nitrogen or argonmay be used.

If desired, the polymerization process may further comprise the steps ofisolating the resulting polymer from the solvent, monomer, andinitiators system, and may further comprise the step of recovering andrecycling the initiator and transition metal complex of the initiatorsystem. The transition metal may be isolated by many techniques known inthe art including addition of a solvent in which the transition metalcomplex is insoluble, addition of a ligand that reduces the solubilityof the transition metal complex in a chosen solvent, filtration withsilica, alumina or Celite, and centrifugation. In many instances, it ispreferred to further functionalize the azlactone terminal group prior toseparation of the transition metal complex as many separationtechniques, such as contact with silica, can result in ring-opening ofthe azlactone group. Thus it is preferred to first react the product(co)polymer with a compound of the formula R⁵(ZH)_(m) to functionalizethe terminal azlactone group prior to isolation of the transition metalcomplex, as previously described.

The (co)polymers obtained by the method of the invention may bedescribed as telechelic (co)polymers comprising polymerized units of oneor more free radically (co)polymerizable monomers (as previouslydescribed), a first azlactone terminal group derived from the initiatorof Formula I and a second terminal group selected from the group derivedfrom X. Alternatively, when using the initiators of Formula II, thefirst terminal group “Az” will comprise the ring-opened residue of theazlactone group of the Formula III:

-   -   where R¹, R², R³, R⁴, R⁵, Z, Q and n are as previously defined.

Such (co)polymers have the general formula Az-(M¹)_(x)(M²)_(x)(M³)_(x) .. . (M^(Ω))_(x)-X, wherein X is Cl, Br or a pseudohalogen group,

M¹ to M^(Ω) are each polymerized monomer units derived from a radically(co)polymerizable monomer unit having an average degree ofpolymerization x,

each x is independent, and Az is an azlactone group or a ring-openedazlactone group of Formula III. Further, the polymer product retains thefunctional group “X” at one terminal end of the polymer necessary toinitiate a further polymerization (or functionalization). The polymerproduct further comprises either the azlactone moiety or the ring-openedazlactone moiety of the initiator at the other terminal end, which maybe further reacted or functionalized as desired. Because the twoterminal moieties have different functionality and reactivity, eachterminus may be independently functionalized.

The terminal “X” group may be functionalized independently from theterminal “Az” group. For example, where X is Br, the terminal brominemay be reduced to a hydrogen by treatment with Bu₃SnH, may be convertedto an acyl group by treatment with a trimethylsilyl vinyl ether, and maybe converted to an azide by treatment with NaN₃, which in turn may beconverted to an amine by reduction with LiAlH₄. Other methods ofconverting a terminal halide group to other functional groups are knownin the art, and reference may be made to Chem. Rev., vol. 101, pp.2921-2990, 2001.

The present invention encompasses a novel process for preparing random,block, multi-block, star, gradient, random hyperbranched and dendriticcopolymers, as well as graft or “comb” copolymers. Each of thesedifferent types of copolymers will be described hereunder.

Since ATRP is a “living” or “controlled” polymerization, it can beinitiated and terminated as desired. Thus, in one embodiment, once thefirst monomer is consumed in the initial polymerizing step, a secondmonomer can then be added to form a second block on the growing polymerchain in a second polymerizing step. Additional polymerizations with thesame or different monomer(s) can be performed to prepare multi-blockcopolymers. The subsequent polymer steps may use the same initiatorsystem as in the first step of the polymerization, or another may bechosen to reflect or “match” the different reactivity of the subsequentmonomers.

Because ATRP is radical polymerization, blocks can be prepared inessentially any order. One is not necessarily limited to preparing blockcopolymers where the sequential polymerizing steps must flow from theleast stabilized polymer intermediate to the most stabilized polymerintermediate, such as is necessary in ionic polymerization. Thus, onecan prepare a multi-block copolymer in which a polyacrylonitrile or apoly(meth)acrylate block is prepared first, then a styrene or butadieneblock is attached thereto, etc.

Furthermore, a linking group is not necessary to join the differentblocks of the present block copolymer. One can simply add successivemonomers to form successive blocks. Further, it is also possible (and insome cases advantageous) to first isolate a (co)polymer produced by thepresent ATRP process, then react the polymer with an additional monomerusing a different initiator/catalyst system (to “match” the reactivityof the growing polymer chain with the new monomer). In such a case, theproduct polymer having a terminal “X” group acts as the new initiatorfor the further polymerization of the additional monomer. Since thenovel initiators provide a reactive group “Az” at a terminal end of thepolymer, linking groups may be used to join two polymer blocks. Forexample, in one embodiment, a polymer prepared in accord with thepresent invention, and having an azlactone group at one terminus, may bereacted with a second polymer block having a nucleophilic terminalgroup.

Statistical copolymers may be produced using the initiators of thepresent invention. Such copolymers may use 2 or more monomers in a rangeof about 0-100% by weight of each of the monomers used. The productcopolymer will be a function of the molar amounts of the monomers usedand the relative reactivity of the monomers.

The present invention also provides graft or “comb” copolymers. Here, afirst (co)polymer having pendent nucleophilic functional groups, suchhydroxy-, amino- or thio-groups, etc. is provided. An example of auseful (co)polymers include hydroxyethyl acrylate (co)polymers. Next,the reactive functional groups of the first (co)polymer is reacted withthe azlactone initiators of Formula I to provide a (co)polymer havingpendent, ring-opened initiator moieties, the reaction product having thestructure of Formula II, where R⁵ is the residue of the first(co)polymer. This product (co)polymer may then be used as an initiatorto polymerize the previously-described monomers to produce a comb(co)polymer. Alternatively, the first (co)polymer may be reacted with atelechelic (co)polymer of the invention, whereby the reactive “Az”terminal group reacts with the pendent reactive group of the first(co)polymer.

Gradient or tapered copolymers can be produced using ATRP by controllingthe proportion of two or more monomers being added. For example, one canprepare a first block or an oligomer of a first monomer, then a mixtureof the first monomer and a second distinct monomer can be added inproportions of from, for example, 1:1 to 9:1 of first monomer to secondmonomer. After conversion of all monomer(s) is complete, sequentialadditions of first monomer-second monomers mixtures can providesubsequent “blocks” in which the proportions of first monomer to secondmonomer vary. Thus, the invention provides copolymers obtained from twoor more radically (co)polymerizable monomers wherein the copolymer has acomposition that varies along the length of the polymer chain fromazlactone terminus to opposite terminus based on the relative reactivityratios of the monomers and instantaneous concentrations of the monomersduring polymerization

EXAMPLES

All reagents unless otherwise noted were purchased from Aldrich(Milwaukee, Wis.) and were used in their delivered condition.Polymerizable reagents were stripped of inhibitors prior to use bypassing them through an alumina column (also supplied by Aldrich).Solvents were purchased from EM Science located in Gibbstown, N.J.

Glossary

-   “bpy” means bipyridyl;-   “MMA” means methyl methacrylate;-   “PMMA” means poly(methyl methacrylate);-   “P” means polydispersity index;-   “bromo-di-methyl azlactone” means 2-(1-bromo-1-methyl    ethyl)-4,4-dimethyl-4H-oxazol-5-one;-   “DBU” means 1,8-diazabicyclo[5.4.0]undec-7-ene; and-   “GPC” means gel permeation chromatography.

Example 1

Preparation of 2-(2-bromopropionylamino)-2-methylpropionic Acid.

X=Br, R¹=H, R²=CH₃

To a stirring mixture of 2-aminoisobutyric acid (52.08 g, 0.51 mol),sodium hydroxide (20.20 g, 0.51 mol), 200 mL water, and 50 mL chloroformcooled to −12° C., was added a solution of 2-bromopropionyl bromide (100g, 0.46 mol) in 150 mL chloroform over 15 minutes. The temperature wasmaintained between −15 and −12° C. during the addition. The reactionmixture was then allowed to warm to room temperature and theprecipitated solid was filtered. The solid was mixed with 700 mL hottoluene, and then cooled. The white solid was then filtered and driedunder vacuum. A yield of 77.60 g (70%) was obtained.

Example 2

Preparation of 2-(1-bromoethyl)-4,4-dimethyl-4H-oxazol-5-one.

X=Br, R¹=H, R²=CH₃

To a stirring mixture of 2-(2-bromopropionylamino)-2-methyl propionicacid (50.00 g, 0.21 mol), triethylamine (23.37 g, 0.23 mol), and 150 mLacetone cooled to 5° C., was added dropwise a solution of ethylchloroformate (25.07 g, 0.23 mol) in 40 mL acetone. After full addition,the mixture was allowed to warm to room temperature, and was stirred fortwo hours. The mixture was filtered, and the solid was washed withether. The solvent was then removed under vacuum, and the residue wasfiltered. The filtrate was distilled under reduced pressure to give acolorless oil (bp 63-64° C. at 1 mmHg). A yield of 34.73 g (75%) wasobtained.

Example 3

Preparation of 2-(2-chloro acetylamino)-2-methyl Propionic Acid.

X=Cl, R¹=R²=H

To a stirring mixture of 2-aminoisobutyric acid (165.8 g, 1.61 mol),sodium hydroxide (64.4 g, 1.61 mol), and 800 mL water cooled to 5° C.,was added two separate solutions of chloroacetyl chloride (200 g, 1.77mol) and sodium hydroxide (70.8 g, 1.77 mol) in 143 mL water. Thetemperature was maintained between 5 to 10° C. during the addition. Thereaction mixture was then allowed to warm to room temperature and thesolution was acidified with 165 mL of concentrated aq. HCl. Theprecipitated solid was filtered and dried under vacuum. A yield of 180.4g (62%) was obtained.

Example 4

Preparation of 2-(chloromethyl)-4,4-dimethyl-4H-oxazol-5-one.

X=Cl, R¹=R²=H

To stirring mixture of 2-(2-chloro acetylamino)-2-methyl propionic acid(18.04 g, 0.10 mol), triethylamine (11.13 g, 0.11 mol), and 100 mL ofacetone cooled with an ice bath was added ethyl chloroformate (10.52 mL,0.11 mol) over 10 minutes. The reaction mixture was warmed to roomtemperature and stirred for 2 hours. The mixture was then filtered, andthe filtrate was concentrated under vacuum. Hexane (200 mL) was added tothe residue and the mixture was filtered. After removal of the solventunder vacuum, the residue was distilled under reduced pressure (bp59-60° C. at 7 mmHg) to give a colorless oil. A yield of 13.18 g (82%)was obtained.

Example 5

Preparation of 2-(2-bromo-2-methyl propionylamino)-2-methyl-propionicAcid.

X=Br, R¹=CH₃, R²=CH₃

A stirring mixture of 2-aminoisobutyric acid (28.5 g, 0.28 mol), sodiumhydroxide (11.1 g, 0.28 mol), 115 mL of water, and 30 mL of chloroformwas cooled to −10° C. and stirred vigorously while a solution of2-bromisobutyryl bromide (57.0 g, 0.25 mol) in 85 mL of chloroform wasadded dropwise. When addition was complete, the reaction flask wasremoved from the cold bath and allowed to warm to room temperature. Themixture stirred for 15 hours. Concentrated HCl (10 mL) was then added tothe mixture and stirring was continued for another 30 minutes. A whitesolid (32.0 g) was filtered off, and the aqueous and organic phases ofthe filtrate were separated. The organic phase was dried over magnesiumsulfate, filtered, and evaporated at reduce pressure to leave a whitesolid (21.0 g). The two solid portions were combined and recrystallizedfrom toluene to afford 27.1 g (43%) of the title compound as a whitesolid with IR and NMR spectra consistent with the desired product.

Example 6

Preparation of 2-(1-bromo-1-methyl ethyl)-4,4-dimethyl-4H-oxazol-5-one.

X=Br, R¹=CH₃, R²=CH₃

A solution of ethyl chloroformate (32.4 g, 0.30 mol) in 50 mL acetonewas added dropwise to a stirring mixture of 2-(2-bromo-2-methylpropionylamino)-2-methylpropionic acid (67.9 g, 0.27 mol) andtriethylamine (30.0 g, 0.30 mol) in 200 mL of acetone at −15° C. Whenaddition was complete, the mixture was stirred at room temperature for 2hours, and the white solid was filtered off and washed with 100 mL ofether. The combined filtrates were reduced in volume to about 200 mL atreduced pressure and cooled in a refrigerator at about 5° C. overnight.The small amount of white solid that had separated was removed byfiltration, and the solvents were evaporated at reduced pressure. Theresidue was taken up in 300 mL of ether, filtered, and the solventevaporated to leave the title compound (61.5 g, 98%) with IR and NMRspectra consistent with the desired product.

Example 7

Preparation of 2-(2-bromo-2-methyl propionylamino)-2-methyl propionicAcid 2,2-bis-[2-(2-bromo-2-methyl propionylamino)-2-methylpropionyloxymethyl]-butyl Ester.

R¹, R²=CH₃, X=Br

A mixture of 2-(1-bromo-1-methyl ethyl)-4,4-dimethyl-4H-oxazol-5-one(17.3 g, 74 mmol), trimethylolpropane (3.30 g, 24.6 mmol), andtrifluoroacetic acid (0.10 g, 0.9 mmol) was heated in a sealed vessel at75° C. for 17 hours. The resulting product, a white solid, wasrecrystallized twice from aqueous ethanol to afford the title compound(12.7 g, 62%) as a white solid with IR and NMR spectra consistent withthe desired product.

Example 8

Controlled Polymerization of Methyl Methacrylate.

In a 50 mL three-necked reaction vessel equipped with manual stirring,N₂ inlets and outlets, and a thermocouple, MMA (21.025 g, 210 mmol),bromo-di-methyl azlactone (0.94 g, 4 mmol), and bpy (1.88 g., 12 mmol)were stirred and purged with N₂ for a period of 30 minutes. The solutionwas also heated to 70° C. via an oil bath powered by a J-Kem digitaltemperature controller. CuCl (0.392 g., 4 mmol), stored and weighed inan inert atmosphere, was added such that the molar ratios of thereagents used were monomer:initiator:CuCl:ligand=105:2:2:6. Thetheoretical M_(n) of the final polymer at 100% conversion using thisratio was about 5,300 g/mol. The reaction was allowed to proceed for 70minutes.

A syringe was used to take aliquots of the mixture through a rubbersepta as time passed. The aliquots were immediately quenched in a largeexcess of methanol. The precipitate was then filtered, dried andsubmitted for GPC.

The results of the polymerization of MMA are shown in Table 8.1.

TABLE 8.1 GPC data for ATRP of MMA using bromo dimethyl azlactone. Time(min.) M_(w) (10⁻³) M_(n) (10⁻³) P 10 1.87 1.73 1.08 20 2.86 2.45 1.1730 2.97 2.38 1.25 40 3.29 2.57 1.28 50 3.51 2.71 1.29 60 3.95 3.05 1.2970 5.10 3.90 1.31

The data in Table I demonstrates that the molecular weight increasessteadily over time and that the polydispersity is <1.1 at lowerconversions and increases to 1.3 at higher conversions. Thesecharacteristics are indicative of a living/controlled polymerizationprocess.

Example 9

Use of a Multi-Functional Initiator to Synthesize Poly(methylmethacrylate) PMMA Star Polymers.

A 100 mL three-necked reaction vessel, equipped with manual stirring, N₂inlets and outlets, and a thermocouple, and was charged with MMA, 21.025g, 210 mmol), the initiator of Example 7 (1.115 g, 4 mmol), toluene (46g, 33 wt.% solids) and bpy (1.88 g, 12 mmol). The solution were stirredand purged with N₂ for a period of 30 minutes, then heated to 50° C. viaan oil bath powered by a J-Kem digital temperature controller. CuCl(0.392 g, 4 mmol), stored and weighed in an inert atmosphere, was addedsuch that the molar ratios of the reagents used weremonomer:initiator:CuCl:ligand=105:2:2:6. The theoretical M_(n) of thefinal polymer at 100% conversion using this ratio was about 16,000 g/molor about 5,300 g/mol per arm. The reaction was allowed to proceed for 6hours.

The M_(n), as determined by GPC, of the resulting poly(MMA) star polymerwas 16,400, which compared favorably to the theoretical value.Furthermore, the star polymer had a polydispersity, P, of 1.24.

Example 10

Using a Functional Initiator to Yield Star Polymers Through ChemicalModification.

Linear PMMA arms were synthesized according to the methods taught inExample 8 and GPC was used to confirm the M_(n) of the polymer to be10,300 g/mol (P=1.18). In a 9-dram glass vial, tris-aminoethyl amine(0.0142 g, 9.7×10⁻⁵ mol) was added to a 33 wt. % toluene solutioncontaining 3.00 g. (2.91×10⁻⁴ mol) of functional PMMA arms. The vial wascapped and placed in a heated shaker bath at 60° C. for 16 hours. Theresulting star polymer had a M_(n) of 34,900 g/mol and P=1.10 asdetermined by GPC.

Example 11

Using a Functional Initiator to Yield Star Polymers Through ChemicalModification.

Linear PMMA arms were synthesized according to the methods taught inExample 1 and GPC was used to confirm the M_(n) of the polymer to be10,300 g/mol (P=1.18).

In a 9-dram glass vial, tris-aminoethyl amine (0.0142 g, 9.7×10⁻⁵ mol)was added to a 33 wt. % toluene solution containing functional PMMA(3.00 g, 2.91×10⁻⁴ mol) arms. A catalytic amount of DBU was added to aidin reaction completion. The vial was capped and placed in a heatedshaker bath at 60° C. for 16 hours. The resulting star polymer had aM_(n) of 30,500 g/mol and P=1.11 as determined by GPC.

Example 12

Using a Functional Initiator to Synthesize Block Copolymers.

A three-armed PMMA macro-initiator was synthesized according to themethods taught in Example 9. The macro-initiator possessed a Mw of37,000 g/mol and a M_(n) of 18,800 g/mol. In a 100 mL three-neckedreaction vessel equipped with manual stirring, N₂ inlets and outlets,and a thermocouple, three-armed PMMA macro-initiator (9.69 g, 0.515mmol), n-butyl acrylate (10.92 g, 0.085 mol), toluene (40 g, 33 wt. %solids) and bpy (0.724 g, 4.6 mmol) were stirred and purged with N₂ fora period of 30 minutes. The solution was heated to 70° C. by an oil bathpowered by a J-Kem digital temperature controller. CuCl (0.1529 g, 1.5mmol), stored and weighed in an inert atmosphere, was added such thatthe molar ratios of the reagents used weremonomer:initiator:CuCl:ligand=120:1:3:9. The reaction was allowed toproceed for 8 hours. After moderate conversion, the block copolymer wasdetermined by GPC to possess a Mw of 50,700 g/mol and a M_(n) of 26,300g/mol.

Example 13

Controlled Polymerization in Real-Time by IR Spectroscopy.

A ReactIR 1000 (ASI Applied Systems, Millersville, Md.) infra-redspectrometer, was fitted with a silicon ATR probe to provide IR spectrain real time and in-situ. The data was processed to give the kineticparameters of the system. The procedure is similar to a conventional labscale polymerization with the exception of the incorporation of an IRprobe into the solution. The IR spectrometer scanned the solution at setintervals and stored the spectra to obtain quantitative data related tothe appearance and disappearance of various species. Also, the spectrashow the azlactone had not been ring-opened and remained reactive. Inparticular, the intensity of the carbon-carbon double bond stretchingvibration in acrylate-related monomers is directly proportional to theconcentration of the monomer in solution. Thus recording the intensityvs. time can provide kinetic information on a vinyl polymerization.

In a 250 mL three-necked reaction vessel equipped with manual stirring,N₂ inlets and outlets, and a thermocouple, and an IR probe,methylmethacrylate (26.4 g), (2-bromo-di-methyl azlactone (1.153 g),toluene (26.4 g) and bpy (2.1 g) were stirred and purged with N₂ for aperiod of 30 minutes. The solution was also heated to 70° C. via an oilbath powered by a J-Kem digital temperature controller. An initial IRscan was taken as a start point of the reaction. CuCl (0.4953 g), storedand weighed in an inert atmosphere, was added immediately after thespectrum was completed.

The intensity of the vinyl peak at 1640 cm⁻¹ was monitored at intervalsof 30 seconds to 5 minutes over a total reaction time of 8 hours. A plotof ln(M₀/M) vs. time (where M₀ is the initial concentration of monomerand M is the concentration at time t) for data out to 340 minutesyielded a straight line with R²=0.9998. Beyond this point, the reactionis >95% complete. This indicates that the polymerization is first orderin monomer.

1. A controlled radical polymerization initiator comprising: a) acompound of the formula:

wherein X is Cl, Br, or a pseudohalogen group; R¹ and R² are eachindependently selected from X, H, an alkyl group, a cycloalkyl group, aheterocyclic group, an arenyl group and an aryl group, or R¹ and R²taken together with the carbon to which they are attached form acarbocyclic ring; R³ and R⁴ are each independently selected from analkyl group, a cycloalkyl group, an aryl group, an arenyl group, or R³and R⁴ taken together with the carbon to which they are attached form acarbocyclic ring containing 4 to 12 ring atoms; n is 0 or 1; Z is O, NH,S or NR⁶, wherein R⁶ is a C₁ to C₆ alkyl group; R⁵ is an organic moietyand has a valency of m, or an organic or inorganic solid suport; Q is alinking group selected from a covalent bond, (—CH₂—)_(o),—CO—O—(CH₂)_(o)—, —CO—O—(CH₂CH₂O)_(o)—, —CO—NR⁶—(CH₂)_(o)—,—CO—S—(CH₂)_(o)—, where o is 1 to 12, and R⁶ is H, an alkyl group, acycloalkyl group, an arenyl group, a heterocyclic group or an arylgroup; and m is an integer of at least
 2. 2. The initiator of claim 1wherein at least one of R¹ and R² is a C₁ to C₄ alkyl group.
 3. Theinitiator of claim 2 wherein R¹ and R² are methyl.
 4. The initiator ofclaim 1 wherein at least one of R³ and R⁴ is a C₁ to C₄ alkyl group. 5.The initiator of claim 4 wherein R³ and R⁴ are methyl.
 6. The initiatorof claim 1 wherein Q is a covalent bond.
 7. The initiator of claim 1wherein R⁵-Z- is the residue of a mono- or polyfunctional compound ofthe formula R⁵(ZH)_(m) wherein Z is —O—, —S—, or —NR⁶ is H, an alkyl, acycloalkyl or aryl, a heterocyclic group, an arenyl and m is at leastone.
 8. The initiator of claim 1 wherein R⁵ is a solid support.
 9. Theinitiator of claim 1 wherein R⁵ is an aliphatic, cycloaliphatic,aromatic of alkyl-substituted aromatic moiety having from 1 to 30 carbonatoms.
 10. The initiator of claim 1 wherein R⁵ comprises apolyoxyalkylene, polyester, polyolefin, polyacrylate, or polysiloxanepolymer.
 11. The initiator of claim 8, wherein said solid support is inthe form of a plurality of particles or a membrane.
 12. The initiator ofclaim 11, wherein said solid support comprises polystyrenes,polyalkylenes, nylons, polysulfones, polyacrylates, polycarbonates,polyesters, polyimides, polyurethanes having hydroxyl, amino or thiolsubstituents on the surface thereof.
 13. The initiator of claim 1wherein R⁵ comprises silica, alumina or glass having a plurality of -ZHgroups on the surface therof.
 14. The initiator of claim 1, wherein R5is derived from a polymer having a valence of m, and a plurality ofnucleophilic -ZH groups.